short-course radiotherapy followed by chemotherapy and pd-1 inhibitor for locally advanced rectal cancer

Conditions: Rectal Neoplasms Malignant; Radiotherapy

Summary: this phase ii/iii trial studies how well neoadjuvant short-course radiotherapy and chemotherapy with or without pd-1 inhibitors works in treating patients with locally advanced rectal adenocarcinoma. neoadjuvant short-course radiation therapy followed by two-drug regimen chemotherapy, such as capox, were shown to be non-inferior to standard long-course chemoradiotherapy in our previous stellar study. immune checkpoint inhibitors (icis) using monoclonal antibodies, such as pd-1 or pd-l1 inhibitor, show promising efficiency and reliable security in some limited sample prospective or retrospective studies. when treating patients with locally advanced rectal cancer, giving sequential neoadjuvant short-course radiotherapy and chemotherapy with pd-1 inhibitor may work better.


Eligibility criteria:
inclusion criteria: * biopsy proven rectal adenocarcinoma; * distance between tumour and anal verge≤ 10cm; * locally advanced tumour;(8th edition ajcc/uicc staging :ct3-t4n0/ct2-4n+，m0) cancer staging must be based on pelvic mri or endoscopic ultrasound; * eastern cooperative oncology group(ecog) performance score ≤ 1; * mentally and physically fit for chemotherapy; adequate blood counts: white blood cell count ≥3.5 x 109/l haemoglobin levels ≥100g/l platelet count ≥100 x 109/l creatinine levels ≤1.0× upper normal limit（unl） urea nitrogen levels ≤1.0× upper normal limit（unl） alanine aminotransferase(alt) ≤1.5× upper normal limit（unl） aspartate aminotransferase(ast) ≤1.5× upper normal limit（unl） alkaline phosphatase(alp) ≤1.5× upper normal limit（unl） total bilirubin(tbil) ≤1.5× upper normal limit（unl） * no excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis. * no previous pelvic radiation history； * written informed consent; exclusion criteria: * previous treatment with anti-pd-1/l1 and anti-ctla-4 or other immune experimental drugs. * severe autoimmune disease: active inflammatory bowel disease (including crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g. wegener's granulomatosis) * symptomatic interstitial lung disease or active infectious/non-infectious pneumonia. * at risk for bowel perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (gi) obstruction, abdominal cancer or other known risk factors for bowel perforation. * history of other malignancies, excluding curable non-melanotic skin cancer and cervix carcinoma in situ； * active infection, heart failure, heart attack within 6 months, unstable angina or unstable arrhythmia. * any condition investigator considered may interfere with the results or place the patient at increased risk of treatment complications, or other uncontrollable disease. * pregnancy or breast feeding * immunodeficiency disorders including human immunodeficiency virus (hiv), or history of organ transplantation, allogeneic stem cell transplantation * active hepatitis b virus (hbv) hepatitis (hbv-dna ≥ 2000 u/ml), hepatitis c virus (hcv) hepatitis, active tuberculosis infection. * oncology vaccination history or any vaccination within 4 weeks prior to the start of treatment.(note: influenza vaccines are mostly inactivated and therefore allowed, intranasal preparations are usually live attenuated vaccines and therefore not allowed) * concomitant other immune agents, chemotherapeutic agents, other drugs in clinical studies, and long term cortisol application

Keywords: rectal cancer short-course radiotherapy total neoadjuvant therapy pd-1 inhibitor